Enantioselective guest exchange in a chiral resorcin[4]arene cavity

Gas-phase proton-bound complexes between a chiral resorcin[4]arene and some representative amino acids, that is, L- and D-alanine or L- and D-serine, were generated in the source of a Fourier transform ion cyclotron resonance mass spectrometer. Gas-phase exchange of the amino acid from the diastereomeric complexes with the enantiomers of 2-butylamine exhibits a significant enantioselectivity, which depends not only upon the configuration of the leaving guest but also on that of the incoming amine. These findings, coupled with molecular dynamic calculations, point to the observed gas-phase enantioselectivity as determined by the effects of the resorcin[4]arene chiral cavity upon the diastereomeric exchange transition structures.     

Exceptional gas-phase enantioselectivity of chiral tetramide macrocycles

Diastereomeric proton-bound complexes between some phenylalanine derivatives (A) and chiral tetramide macrocycles (M) exhibit an uncommon enantioselectivity when reacting with the enantiomers of 2-aminobutanes in the gas phase (B). The measured enantioselectivity depends mainly on two distinct factors: (i) the configuration of the A guest; and (ii) the structure and the relative stability of isomeric [MHA]+ complexes. No significant effects of the B configuration are observed. The diastereomeric [MHA]+ complexes with A = 1-naphthylalanine ethyl ester exhibit the largest enantioselectivity factor ever measured in the gas phase (khomo/khetero = 0.046). The origin of such an exceptional enantioselectivity is mainly attributed to the relative stability of the diastereomeric [MHA]+ complexes, as demonstrated by the comparison of the kinetic results with those from collision-induced dissociation of the trimeric [M2HA]+ adducts and with computational evidence.     

PHOTOREACTION OF PSORALEN DERIVATIVES WITH STRUCTURALLY ORGANIZED DNA

Abstract— The DNA-photobinding process of a number of psoralen derivatives has been investigated using different nucleic acid structures, such as double helical DNA, nucleosomes, and chromatin under various ionic strength conditions. Important differences were observed using "free" vs organised DNA as the target macromolecule, which are related to conformational, stereochemical, ionic and competition effects. The furocoumarin chemical nature also plays a role; in particular, charged compounds are shown to be more reactive than uncharged analogues with free DNA at low salt concentration, whereas a levelling off in photobinding efficiency occurs on increasing ionic strength and nucleic acid complexity. These results allow an explanation for the photobiological effects of the examined psoralens.     

Solid-state structure and conformation of (Z)-2-(phenylbenzylidene)-3-quinuclidinone,an intermediate in the synthesis of quinuclidine derivatives

(Z)-2-(2-phenylbenzylidene)-3-quinuclidinone, C₂₀H₁₉NO,M _r =300.47D crystallizes in the monoclinicP2₁/c space group witha = 6.9809(2) Å,b=19.0523(2) Å,c = 11.7733(1) Å,=100.92(2)°,V=1537.5(3) ų,Z=4,D _c = 1.298 g/cm³,D _x =1.29 g/cm³ (flotation). Diffractometric data, using CuK radiation,=1.54178 Å, were collected on plate-like crystals. The structure, solved by direct methods was refined to a final R value of 0.037 for the 2645 observed reflections withF _o >3.0(F _o ). The molecule shows a trans conformation around the double bond. The quinuclidine and the diphenyl moieties present deformations in their geometric and conformational parameters due to the need of releasing intramolecular strains and/or nonbonded interactions.     

Study of binding affinity and selectivity of perylene and coronene derivatives towards duplex and quadruplex DNA by ESI‐MS

In this paper, we report an extensive electrospray ionization mass spectrometry (ESI‐MS) study of the noncovalent interactions between different intermolecular and intramolecular G‐quadruplex structures and several perylene and coronene ligands. The selectivity of these compounds toward quadruplex structures with respect to duplex DNA, a fundamental topic for the biological evaluation and the pharmacological application of these ligands as potential chemotherapeutic agents, has also been investigated. After exploring this topic according to the classical approach based on the very simple duplex model of an autocomplementary dodecamer, we extended our analysis reporting for the first time a competition ESI‐MS experiment in the presence of genomic DNA fragments. Whereas those ligands showing a high level of selectivity between quadruplex and duplex oligonucleotides, in terms of binding constants and percentage of bound DNA, confirmed their selectivity in the competition experiment, the contrary was not always true: some ligands showing poor selectivity with the autocomplementary dodecamer resulted selective in the presence of genomic DNA fragments. This result suggests that physiologically nonrelevant interactions are possible with a short duplex oligonucleotide. This means that the dodecamer can fail in representing a biologically significant structural model, or, better, that it can be used to quickly screen potentially selective molecules, but bearing in mind the high probability of false negative results. Copyright © 2008 John Wiley & Sons, Ltd.     

Metal bioavailability in marine sediments measured by chemical extraction and enzymatic mobilization

In this work we compared metal bioavailable fractions in marine sediments operationally measured by sequential selective extractions (in particular the labile fraction released by acetic acid) and by a biomimetic approach using a commercially available proteolytic enzyme, proteinase K, chosen because of its non-specific behaviour and because it is representative of the enzymes encountered in many deposit-feeding organisms. Different experimental conditions for enzymatic extraction were investigated and the enzyme was employed both untreated and thermally denatured to study metal release mechanisms (i.e. enzymatic hydrolysis and/or complexation). Extractable protein content was also measured to verify possible correlations with some metals.Considering the two sediments used in this work, the available fraction evaluated with a biomimetic approach was often significantly lower than the fraction released by the first step of selective extractions, as expected. Moreover a good correlation was found between the fraction of metal available to the enzyme and enrichment factors in the gut fluids of deposit-feeding organisms, suggesting that enzymatic approach is qualitatively more reliable than chemical extraction in replicating the mechanism of metal mobilization that occurs in the guts of deposit-feeders.     

Enantioselective Supramolecular Carriers for Nucleoside Drugs. A Thermodynamic and Kinetic Gas Phase Investigation

The enantioselective interactions between chiral tetra-amidic receptors and nucleosides have been investigated by the ESI-IT-MS and ESI-FT-ICR-MS methodologies. Configurational effects on the CID fragmentation of diastereomeric [M ^H ₂ ?H?A]?⁺ aggregates (A?=?2'-deoxycytidine dC, citarabine (ara-C) were found to be mostly offset by isotope effect in [S ^X ₂ ?H?A]?⁺ (X?=?H, D) differently from the results obtained on the analogues (A?=?cytidine C and gemcitabine G). This result points the involvement of two different nucleoside/tetraamide isoforms. The structural differences of the [M ^H ₂ ?H?A]?⁺ (A?=?C and G) complexes vs. the [M ^H ₂ ?H?A]?⁺ (dC and ara-C) ones is fully confirmed by the kinetics of their uptake of the 2-aminobutane enantiomers, measured by FT-ICR mass spectrometry. Indeed, uptake of the 2-aminobutane enantiomers by [M ^H _n ?H?A]?⁺ (n?=?1,2; A?=?dC and ara-C) complexes is reversible, while that by [M ^H _n ?H?A]?⁺ (n?=?1,2; A?=?C and G) is not. The most encouraging result concerning the measured fragmentation and kinetic differences between C and ara-C, that are just epimers, indicates the possibility to subtly modulate the non-covalent drug/receptor interactions, through the electronic properties of the 2'-substituent on the nucleoside furanose ring, and furthermore on its three-dimensional position.     

Cyclochiral resorcin[4]arenes as effective enantioselectors in the gas phase

The effect of cyclochirality of rccc-2,8,14,20-tetra-n-decyl-4,10,16,22-tetra-O-methylresorcin[4]arene (C) on the enantiodiscrimination of a number of chiral bidentate and tridentate aromatic and aliphatic biomolecules (G) has been investigated by nano-electrospray ionization (nano-ESI)-Fourier transform ion cyclotron resonance mass spectrometry. The experimental approach is based on the formation of diastereomeric proton-bound [C·H·G](+) complexes by nano-ESI of solutions containing an equimolar amount of quasi-enantiomers (C) together with the chiral guest (G) and the subsequent measurement of the rate of the G substitution by the attack of several achiral and chiral amines. In general, the heterochiral complexes react faster than the homochiral ones, except when G is an aminoalcoholic neurotransmitter whose complexes, beyond that, exhibit the highest enantioselectivity. The kinetic results were further supported by both collision-induced dissociation experiments on some of the relevant [C(2) ·H·G](+) three-body species and Density functional theory (DFT) calculations performed on the most selective systems.     

First measurements of inclusive muon neutrino charged current differential cross sections on argon

The ArgoNeuT Collaboration presents the first measurements of inclusive muon neutrino charged current differential cross sections on argon. Obtained in the NuMI neutrino beam line at Fermilab, the flux-integrated results are reported in terms of outgoing muon angle and momentum. The data are consistent with the Monte Carlo expectation across the full range of kinematics sampled, 0°<θ(μ)<36° and 0相似文献